Infection with Helicobacter pylori causes a histological gastritis that in some individuals is associated with the development of peptic ulcer disease or gastric malignancy. Although H. pylori may be the most common human bacterial infection, the mechanism by which it is transmitted remains unknown. Person to person transmission probably accounts for most infections. Yet one of the great paradoxes in the epidemiology of H. pylori is that when one examines the gastric lining, the bacterium is ubiquitous, but when fecal or oral secretions are studied it is often difficult to find. This may reflect the difficulty of studying in humans the role of acuity of infection, age of the host, and the possible effects of vomiting, diarrhea, and the CagA pathogenicity island on transmission. Rhesus monkeys are naturally infected with H. pylori that is very similar to strains that infect humans, and this animal model provides a unique opportunity to study experimentally the transmission of H. pylori in a naturally infected host. We hypothesize that acuity of infection, the presence of vomiting and diarrhea, and the CagA pathogenicity island are critical variables in transmission of H. pylori. Furthermore, we propose that there may be a cooperativity between transmission of H. pylori and transmission of bacterial enteric diseases. Diarrheal and vomiting diseases may increase H. pylori transmission by increasing the shedding H. pylori in feces and vomitus, and in turn, H. pylori infection may cause increased gastric pH and thereby promote infection with enteric bacteria by reducing the gastric bactericidal barrier. We propose to address four specific aims in this proposal: l) Determine how H. pylori is shed into the environment during acute and chronic infection; 2) Examine experimentally the effects of vomiting, diarrhea and the CagA pathogenicity island on the natural transmission of H. pylori; 3) Determine the effects of H. pylori infection on the acquisition of Campylobacter jejuni; and 4) Determine the effects of the CagA pathogenicity island on colonization and shedding.